Primary needs in bladder cancer form the focus of this renewal. The primary goal of this study is the identification of probes and features useful in evaluating low grade disease, monitoring therapy, and predicting progression and recurrence through the parallel analysis of DNA, protein expression, and genetic makeup of longitudinally acquired bladder irrigation specimens. Specific aims include: 1) Further defining the utility and role of monoclonal probes shown useful in preliminary and previous studies. Studies will continue utilizing M344, 19A211, T-138, Thomsen-Friedenreich antigen, and Lewis X probes on longitudinally collected bladder irrigation specimens. This study will utilize both slit-scan flow cytometry and fluorescence image analysis. Slit-scan flow cytometry provides quantitative fluorescence together with low resolution morphological information on cells in flow. Collaborative studies with Dr. Yves Fradet will expand the data set. 2) Identification of probes and features useful in monitoring immunotherapy and predicting progression through the parallel analysis of DNA, protein expression, and the genetic makeup of longitudinally acquired bladder irrigation specimens on patients treated with BCG and BCG/IL2. This study will establish relationships between phenotype, genotype, and response to therapy. 3) Identification of chromosomal abnormalities in bladder cancer useful for evaluating low grade disease, obtaining prognostic information on progression and recurrence, and contributing to the understanding of the disease. Studies will continue utilizing peri-centromeric probes for chromosomes 1, 7, 9, 11, and 15 on interphase nuclei. Collaborative studies with Dr. AHN Hopman using standardized fluorescence in situ hybridization methodology and classification criteria will permit combining data sets. This study will be aided by the utilization of new probes supplied by Dr. Joe Gray. 4) A better understanding of FISH data through a study of the statistical aspects of FISH analysis. This includes the detection of low frequency events in a heterogeneous population, the quantized nature of FISH data, and the determination of sensitivity and specificity. Studies will be carried out in continued close collaboration and consultation with clinical colleagues in Urology and with continued strong biostatistical input in all phases to assure statistically meaningful results.